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IAJPS 2018, 05 (02), 890-902 R.

Santosh Kumar and Sahithi Mudili ISSN 2349-7750

CODEN [USA]: IAJPBB ISSN: 2349-7750

INDO AMERICAN JOURNAL OF


PHARMACEUTICAL SCIENCES
http://doi.org/10.5281/zenodo.1181454

Available online at: http://www.iajps.com Review Article

A REVIEW ON TECHNOLOGIES EMPLOYED IN


FORMULATION OF MOUTH DISSOLVING TABLETS
R. Santosh Kumar and Sahithi Mudili
GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam-45.

Abstract:
Oral route is the most preferred route for administration of various drugs because it is regarded as safest, most
convenient and economical route. Recently researcher developed the mouth dissolving tablets with improved patient
compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth
in the absence of additional water for easy administration of active pharmaceutical ingredients. Mouth dissolving
tablets overcome the disadvantages of conventional dosage form especially dysphagia (difficulty in swallowing) in
paediatric and geriatric patients. Mouth dissolving tablets can be formulated by using various technologies like
lyophilization, direct compression, spray drying, molding, nanotization, mass extrusion, sublimation, cotton candy
and phase transition technology along with various patented technologies like zydis,lyoc, flashtab, frosta,
nanocrystal technology, wowtab, durasolv, orasolv advatab and flashdose technology. This review briefly describes
about the various technologies which are used for the formulation of mouth dissolving tablets along with advantages
and limitations of the technology.
Keywords: Mouth dissolving tablets, Patented Technologies, Bioavailability
Corresponding author:
QR code
Dr. R. Santosh Kumar,
GITAM Institute of Pharmacy,
GITAM University,
Rushikonda,
Visakhapatnam-45,
A.P, India.
email:drsantoshrada@gmail.com.
Please cite this article in press as R. Santosh Kumar and Sahithi Mudili., A Review on Technologies Employed In
Formulation of Mouth Dissolving Tablets, Indo Am. J. P. Sci, 2018; 05(02).

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INTRODUCTION:  Mouth dissolving tablets having the benefit of


Mouth disintegrating tablets are useful for pediatric, liquid medication in the solid preparation.
geriatric and also dysphagic patients, who are having  By its pregastric absorption property i.e
the difficulty in swallowing. These dosage forms absorption form mouth, pharynx and
dissolve or disintegrate rapidly in the oral cavity oesophagus it shows rapid onset of action.
within a matter of seconds without the need of water.  It is having improved bioavailability because
A mouth dissolving tablet usually dissolves in the of its pregastric absorption activity.
oral cavity within 15 secs to 3 min. In the recent  It can eliminate the problems like risk of
times, several new advanced technologies have been chocking or suffocation during oral
introduced for the formulation of mouth dissolving administration which is the common problem
tablets for improving the patient compliance by during the administration of conventional
masking the taste of the drug and for increasing the tablets.
bioavailability of the drug. Technologies include  These tablets are more beneficial where rapid
lyophilisation, molding, direct compression, cotton onset of action required in some conditions
candy process, spray drying, sublimation, mass like sudden episodes of allergic attack or
extrusion, nanonization and phase transition. These coughing.
techniques are based on the principles of increasing
porosity and/or addition of superdisintegrants and Limitations of Mouth Dissolving Tablets
water soluble excipients in the tablets. This review  The tablets usually have insufficient
article details the technologies which are useful for mechanical strength. Hence, careful handling
the formulation of mouth dissolving tablets. is required.
 If tablets are not formulated by masking the
Criteria for Formulation of Mouth Dissolving bitter taste of the drug, it can lead to
Tablets unpleasant taste in mouth.
 It should not require water for administration;  Patients which are having decreased saliva
it dissolves and disintegrates rapidly in the production syndrome (Sjogren‘s syndrome)
mouth with in fraction of seconds. are unable to take these mouth dissolving
 It dissolves in the mouth, so it should have tablets.
good mouth feel and taste masking property  Mouth dissolving tablets are sensitive to
 It should have sufficient hardness to with stand moisture (Hygroscopic in nature), so we have
the post manufacturing activities. to store them in dry pace only.
 It should have the capacity to load the high  Mouth dissolving tablets requires special
amount of the drug. packaging conditions for stabilization and
 It should have more bioavailability. safety of the product.
 It should not get affected with environmental
conditions like Temperature and humidity. Technologies Used for Formulation of Mouth
 It should not require special packing. Dissolving Tablets
Following technologies are used for the formulation
Advantages of Mouth Dissolving Tablets of the mouth dissolving tablets. They are
 These tablets can be easily administrated by
the patients like elders who are having the 1.Freeze drying or Lyophilization[1]:
difficulty in swallowing, by children who are The main principle involved in lyophilization or
unable to swallow and by the psychiatric freeze drying technique is removal of water from the
patients who refuse to swallow the tablet. product by freezing. Lyophilization technique is most
 Mouth dissolving tablets are having improved widely used technique in pharmaceutical industries
patient compliance because these tablets can for drying of heat sensitive drugs and biologicals at
be taken by the bed ridden patients and the low temperature under conditions that allows
people who are busy in travelling without need removal of water by sublimation. In this technique
of water. drug is dissolved and dispersed in aqueous solution
 Mouth dissolving tablets are having good carrier and this mixture is poured into the wells of the
mouth feel property because of these property preformed blister packs and this drug solution going
even children also can easily take this to freeze by passing these blister packs in to the
medication. liquid nitrogen freezing tunnel. The tablets
 These tablets can be easily administrated and formulated in this method shows highly porous
having the dose accuracy compared to the nature and increased surface area which leads to
liquid formulation. rapid drug dissolution, increased drug absorption and

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finally shows improved bioavailability of the drug. .the formulation which contains maltodextrins as a
Tablets prepared by lyophilization technique shows matrix forming agent was found to effect the integrity
rapid disintegration within 5 seconds due to quick and strength of the tablets, disintegration time and
penetration of saliva into pores when placed on the pore size. Formulation containing showed the
tongue. Figure -1 explains how lyophilization takes stronger tablets. Xanthan gum and
place by using triple point diagram in which water is hydroxyethylecellulose also showed effect on the
removed from the product after it is frozen and strength and disintegration time of the tablet. The
placed under vacuum, allowing ice to change directly formulation which containing hydroxyethylecellulose
from solid to vapor without passing through liquid as a binder showed less disintegration time compared
phase. to xanthan gum.

Drug example: Advantages:


By taking the Hydrochlorothiazide as a model drug  It is an ideal drying technique for heat
Corveleyn and Remon [2] studied the influence of sensitive products.
various formulation and process parameters on the  Mouth dissolving tablets which are prepared
characteristics of orally disintegrating tablets made by this technique shows very low
by lyophilization technique. They used maltodextrin, disintegration time have good mouth feel due
gelatin, xanthan gum hydroxyethylecellulose as to fast melting effect.
excipients for orally disintegrating tablets preparation Limitations:
and the prepared tablets were evaluated for physical  It is long and cost intensive process.
parameters like hardness, strength,  Tablets prepared by this technique shows poor
porosity,disintegration time and residual moisture stability at higer temparature and humidity.

Fig. 1: Freeze Drying or Lyophilization Method

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2. Molding [3]: by this technique having the good mechanical


In this drug is mixed with water soluble ingredient strength.
with a hydro-alcoholic solvent and molded in to
tablet in conventional tablet compression machine by Drug example:
using the lower pressure compared to less than the Valdecoxib orally disintegrating tablets has been
conventional tablets and then leads to porous nature prepared by Modi and Tayade[4] by using molding or
of the tablet. This porous nature of the tablets helps in solid dispersion method to enhance the dissolution of
the increased drug disintegration and drug dissolution the tablets by kneading the drug with polyvinyl
and finally leads to improved bioavailability. pyrrolidone (PVP K-30) and compressed into tablets.
Molding can be divided into two types. They are The dissolution of the Valdecoxib tablets has been
increased (<85% in 5 minutes) compared to marketed
a) Compression molding: formulations.
Powder blend ismixed with hydroalcoholic solvent
and it is molded into tablet using compression Advantages:
pressure lower than used in conventional tablets  By using molding technique we can prepare
compression. Then solvent present in the molded various sizes and shapes of the tablets.
tablet is removed by air-driying.Figure-2 describes  Mouth dissolving tablets which are prepared by
about the compression molding process, in which molding technique shows porous nature which
preheated molding material is first placed in an open helps in the quick disintegration and dissolution
and preheated mould cavity and pressure is applied to of the tablet when placed on the tongue.
force the material into contact with all mold areas and
gives the molded tablet. Limitations:
 Tablets prepared by molding technique shows
some common problems like Loss in Potency of
tablet, inter tablet migration, sorption by packing
materials and chemical decomposition.

3. Sublimation [5]:
In this drug is mixed with the rapidly volatized
ingredients like camphor ammonium carbonate,
ammonium bicarnonate, hexamethyletetra amine
along with other excipients and this was compressed
into the tablets. After this the formulation undergoes
sublimation to remove the volatized ingredients to
form the porous structure of the tablet. Porous nature
of the tablet helps in the increased drug disintegration
Fig. 2: Compression Molding and drug dissolution and finally leads to improved
bioavailability. Figure: 3 describes about the
sublimation process, in which drug is mixed with
b) Heat molding: excipients and volatilizing agent and compressed in
Iin this technology suspension of drug, agar and to tablets. This compressed tablets undergoes
sugar is prepared and it is going to pour in blister sublimation process in which volatizing agent turns
packing well and solidifying the agar solution at directly into gas without passing into liquid state and
room temperature. Finally a Zell like structure will leads to development of pores on the compressed
form which is dried at approximately 30ºC. tablets. Porous nature of the tablet helps in the quick
disintegration of tablet and leads to improved
c) Molding by vacuum evaporation without bioavailability.
lyophilization:
In this process drug and excipients are mixed and Drug example:
prepared into slurry and poured into mold of desired Orally disintegrating Etoricoxib tablets have been
dimension and going to freeze dry this mixture to developed by Patel and Patel[6] by using sublimation
form a solidified matrix. Then this matrix subjected technique to enhance the dissolution of the drug. In
to vacuum drying at freeze drying temperature and this technique etoricoxib granules have been prepared
result into the formation of tablet. Tablets prepared by using aspartame, menthol, mannitol and
crosspovidone by wet granulation technique. Menthol
was sublimated from the granules by exposing the

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granules to vacuum and resultant porous granules  Taste masking of the drug can be achieved by
were subjected to tableting. The tablets prepared by using spray drying technology.
using this technique showed improved dissolution  It is highly economical process.
profile compared to marketed formulation.
Limitations:
 The drugs which are sensitive to high
temperature cannot be formulated by using
spray drying technology.

Fig. 4: Spray Drying Technique


5. Mass extrusion [8]:
In this method active ingredient is mixed with the
Fig. 3: Sublimation Process solvent mixture of water soluble polyethylene glycol,
4. Spray drying [7]: menthol and expulsion of softened mass through the
Spray drying produces highly porous and fine extruder or syringe to get a cylindrical shape of the
powders that dissolve rapidly. In this technique product into even segments using heated blade to
particulate support matrix is prepared by spray drying from tablets. In this method bitter taste of the drug
an aqueous composition containing support matrix can be easily masked.figure:5 describes about the
and other components to form highly porous and fine mass extrusion technology in which softened mass
powder. This fine powder is then mixed with active extruded from extruder in cylindrical shape and it is
ingredients and compressed into tablets. By cut into even segments.
hydrolyzed and non hydrolyzed gelatins as
supporting agents, mannitol as bulking agent, sodium Advantages:
starch glycolate or croscarmellose sodium as  Fewer processing steps.
disintegrating agent and an acidic material (citric  Shows good disintegration property and
acid) or alkali material (sodium bicarbonate) to increased bioavailability.
enhance disintegration /dissolution. The tablets  By using this technology we can mask the
prepared in this method disintegrate within 20 sec bitter taste of the drug easily.
when immersed in an aqueous medium. Figure:4
describes about spray drying technique in which fluid Limitations:
bed is placed in a reactor and applies hot gas to this  Flow properties of polymers are essential to
fluid bed which leads to the formation of highly processing.
porous and fine powder. This fine powder is mixed
with active ingredient and compressed into tablets.

Advantages:
 Tablets prepared by this method shows the
fastest disintegration time i.e within 20
seconds
 Tablets prepared by this method shows the
porous nature which helps in the fast
disintegration and increased bioavailability of Fig. 5: Mass Extrusion Technique
the drug.

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6. Direct Compression [9]:  Tablets prepared by this method show the


It is most cost effective tablet manufacturing improved bioavailability.
technique. In this active ingredient is mixed with the
other excipients and directly compressed into tablets Limitations:
like conventional tablets. The mixture which is going  Thermo labile drugs cannot be formulated by
to compress into tablets must have good flow using this technology because of high process
properties. In this method we can accommodate high temperature.
doses of the drug. In this method we can use
formulate tablets by using easily available
tablets.Figure:6 describes about the direct
compression method in which blend of API and
excipients and lubricants are mixed and compressed
into tablets by using pressure.

Advantages:
 It is simplest and most cost effective tablet
manufacturing technology.
 Direct compression technique is most suitable
for the moisture and heat sensitive drugs.
Limitations:
 Segregation of API and excipients takes place
because of difference in density.
 Low dilution potential which means directly
compressible materials can accommodate only
30-40 % of the poorly compressible active
ingredients Fig. 7: Cotton Candy Technique

8. Compaction:
a) Melt granulation:
In this method mouth dissolving tablets are
prepared by incorporating the drug into the
hydrophilic waxy binder like PEG-6-Stearate.
Hydrophilic waxy binder helps as binding and
disintegrating agent. The tablets prepared by
this method rapidly dissolve in the mouth
without leaving any residue.

Drug example:
Carbamazepine orally disintegrating tablets
have been developed by Perisuuti et al[11] by
Fig. 6: Direct Compression Technique melt granulation technique. In this technique
7. Cotton Candy Process [10]: carbamezepine granules were developed by
Cotton candy process involves the formation of using PEG 4000 as melting binder and lactose
matrix of polysaccharides by simultaneous action of monohydrate as hydrophilic filler and
flash melting and spinning. This candy floss matrix is crosspovidone as disintegrating agent.
then milled and blended with active ingredients and Carbamazepine granules which are prepared
excipients after recrystallization and subsequently by using this technique showed enhanced in
compressed to mouth dissolving tablets. It can vitro drug dissolution rate.
accommodate high doses of drug and offers improved
mechanical strength.figure-7 describes about the b) Phase transition process:
cotton candy process. In this method two types of sugar alcohols are
used in which one is having the high melting
Advantages: point and other one is having the low melting
 We can accommodate large doses of drugs by point. The compressed powder going to heat in
using this technique. between these melting points and leads to
increased tablet hardness due to increase of

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inert particle bond induced by phase transition 9. Nanonization [13]:


of lower melting points sugar alcohols.figure-8 In this method by using wet milling technique the
describes about the Phase transition process in size of the drug milled into nano size. This milled
which solid changes its phase into liquid by nano sized drug particles are stabilized against
melting and liquid changes its state to gas by agglomeration by surface absorption on selected
vaporization technique. stabilizers and this is formulated into mouth
dissolving tablets. This method is mostly employed
Drug example: for water soluble drugs for increasing the solubility
Kuno et al.[12] studied the effect of type of of the drug which leads to increased bioavailability of
lubricant on the characteristics of orally the drug.
disintegrating tablets manufactured using the
phase transition of sugar alcohols. In this study Advantages:
they used the combination of two sugar  Cost effective manufacturing process.
alcohols, one was erythritol (high melting  Conventional packaging due to exceptional
point sugar alcohol) and second one was durability and wide range of doses.
tetrahalose (low melting point sugar alcohol).
They evaluated the effect of lubricant on the Patented Technologies
characteristics of ODTs manufactured using 1. Zydis (Cardinal Health Inc.)[14]
phase transition mixture of lactose and xylitol In this technology lyophilization of the drug
and magnesium stearate, sodium stearyl takes place in a matrix which consisting of
fumarate and talc as lubricating agents. gelatin. Zydis tablet required special
Among all three lubricants talc was packaging because these tablets are very light
recommended as the most desirable lubricant weight and fragile in nature. Zydis tablet itself
for preparation of ODTs by phase transition of acts as self-preservative, it do not allow the
sugar alcohols. microbial growth in the formulation because
final water concentration in freeze-dried
product is too low. By using this technology
we can formulate both water soluble and water
in soluble drugs as mouth dissolving tablets.
The preferred drugs are water insoluble, low
dose, chemically stable, small particle size and
tasteless.Figure-9 describes about the zydis
technology.

Advantages:
 Mouth dissolving tablets which are produced
by zydis technology shows quick dissolution.
 Tablets prepared by this technology acts as a
self-preserving agents because freeze drying
and shows the increased bioavailability of the
drug.

Limitations:
 It is very expensive process
 Tablets prepared by this technology show the
poor stability at higher temperature and
humidity.
Fig.8: Phase Transition Process

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Fig.9: ZYDIS Technology


2. Lyoc (Cephalon Corporation)[15] low mouldability saccharides (e.g. mannitol,
This technology uses the freeze drying process. In lactose, glucose, sucrose, and erythritol) and
this drug is suspended into liquid solution then granulated with high mouldability
which contains fillers, thickening agents, saccharides (e.g. maltose, maltitol, and
surfactant, non-volatile flavoring agents and sorbitol) and then compressed into tablet. The
sweeteners.This liquid suspension going to tablets prepared by this method dissolve
pour in the blister cavities and subjected to quickly with in 15sec or less.
freeze drying. To prevent in homogeneity by
sedimentation during this process, these Advantages:
formulations require a large proportion of un-  The tablets prepared by using this technology
dissolved inert filler (mannitol), to increase the show the increased dissolution rate and
viscosity of the in process suspension. The hardness.
tablets prepare by this technique are denser in  Mouth dissolving tablets prepared by this
nature. technology provides the good mouth feeling
effect.
Advantages:
 Heat sensitive drugs can be formulated into Limitations:
mouth dissolving tablets by using this  Wow tab technology could not show any
technology. improvement in the Bioavailability of the
drug.
Limitations: 
 Tablets prepared by this technology will have 4. Flashtab (Prographarm)[17]
low mechanical strength. In this technology first drug is coated with a
 In this technology tablets are prepared by eudragit polymer and microencapsulated with
using high portions of fillers which leads to the an effervescent couple to produce flash
reduction in porosity of tablet and resulting dispersal tablet. This technology uses both the
into slower disintegration. methods like wet and dry granulation method
 for the formulation of granules and these
3. Wowtab (Yamanouchi Pharma granules are compressed into tablets. In this
Technologies, Inc.)[16] method super disintegrants plays a main role
‘Wow’ means ‘without water’. In this in the disintegration of the tablet.
technology two types of saccharides are going
to use, in them one is high mouldability Advantages:
saccharide and second one is low mouldability  Flashtab technology purely based on the
saccharide. The drug is going to mix with the conventional tablet technology.

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 It is cost effective technology. Limitations:


 Tablets prepared by this technology  Mouth dissolving tablets which are prepared
disintegrate with in 1 minute in mouth. by this technology shows the low mechanical
Limitations: strength.
 Coating of granules and microencapsulation of 
the drug plays a critical role in this technology. 7. Frosta (Akina)[20]
This technology mainly involves the formulation of
5. Durasolv (Cima Labs, Inc.)[18] plastic granules and compressed them at low
DuraSolv technology is invented by Cima Labs. pressure by using conventional tablets
Durasolv is compatible for low dose drug not technology. Plastic granules composed of
compatible for larger doses drug. In this Porous and plastic material, water penetration
technology high pressure is used for tablet enhancer and binder. The tablets produced by
compaction. Formulation prepared by this this method are strong and having high
technology can be packed into blister packs or porosity nature. Mouth dissolving tablets
vials. DuraSolv tablets consist of active prepared by this method are disintegrates
ingredient, fillers and lubricants. The tablets rapidly within 15 to 30sec.
prepared by this technology have higher
mechanical strength. Advantages:
 Tablets prepared by this technology shows
Advantages: excellent hardness and fast disintegration time.
 By using this technology we can mask the
bitter taste of the drug. 8. AdvaTab (Eurand)[20]
 The tablets prepared by this technology shows In this technology, microencapsulation process is
high rigidity and good mechanical strength. used for coating the drug particles with gastro
soluble polymer so as to mask the taste along
Limitations: with restriction of drug dissolution in mouth
 We can’t accommodate large doses of drugs in cavity. AdvaTab tablets disintegrate rapidly in
to this tablet. the mouth, typically in less than 30 seconds.

6. Orasolv (Cima Labs, Inc.)[19] Advantages:
It based on direct compression of an effervescent  High dose drugs can be formulated into tablets
agent and taste masked drug. The use of by using this technology.
effervescence causes a tablet to disintegrate  Special packaging not required. Tablets can be
rapidly in less than 1 min on contact with packed into both standard bottles and push
water or saliva leaving coated drug powder. through blisters.
This technology can accommodate a wide
range of active ingredient from 1 mg to 500 Limitations:
mg. The effervescence occurs due to chemical  Tablets which are prepared by using this
reaction between organic acid such as Citric technology show decreased mechanical
Acid, Fumaric Acid or Maleic Acid and a base strength.
such as Sodium Bicarbonate, Potassium
Bicarbonate, and Magnesium Bicarbonate, 9. Flashdose (Fuisz Technologies, Ltd.)[21]
which result in generation of CO2. Micro This uses the combination of shear form and
particles, effervescent agents and other ceform technologies in order to mask the bitter
ingredient such as flavors, sweeteners, taste of the drug. Flahdose manufacturing can
colorants and lubricants are blended and be divided into four steps, they are
compressed at a low degree of compaction. 1) Floss blend 2) Floss processing 3) floss
chopping and conditioning 4) tablet blend and
Advantages: compression. Flashdose technology utilizes a
 By using this technology we can mask the unique spinning mechanism to produce a floss-
bitter taste of the drug. like crystalline structure, much like cotton
 Tablets prepared by using this technology candy. This crystalline sugar can then
show the quick dissolution and increased incorporate the active drug and be compressed
bioavailability. into a tablet. It disperses and dissolves quickly.
Instead of a floss-like material, small spheres
of saccharides can be produced to carry the

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drug. The process of making microspheres has  Small doses of the drug can also be formulated
been patented by Fuisz, and is known as into mouth dissolving tablets by using this
ceform and serves as an alternative method of technology.
taste masking. Ceform technology involves
preparation of microspheres of the active drug. 11. Quick-Dis Technology (Lavipharm)[22]
Drug material alone or in combination with Quick-Dis Technology is invented by
other pharmaceutical substances, and Lavipharm laboratories. By using quick-dis
excipients is placed into a rapidly spinning technology can manufacture thin, flexible and
machine. The centrifugal force comes into quick dissolving film. Mouth dissolving film
action, which throws the dry drug blend at when placed on the tongue dissolves rapidly
high speed through small heated openings. on the tongue and helps in the local and
Due to the heat provided by carefully systemic absorption of the drug. Mouth
controlled temperature, drug blend liquefies to dissolving films which are prepared by using
form a sphere, without affecting the drug quick-dis technology shows the quick
stability. The formed microspheres are disintegration time ranges from 5 to 10
compressed into tablet. seconds.

Advantages: 12. EFVDAS (Elan Corporation)[23]


 The tablets prepared by this technology shows EFVDAS technology is a patented technology
increased surface area, which helps in the developed by Elan Corporation. EFVDAS also
increased dissolution of the drug. called as effervescent drug absorption system
which is being used to develop both over to
Limitations: counter (OTC) and prescription medications.
 Drugs which are sensitive to heat, moisture EFVDAS technology has been modified by
and humidity cannot be formulated into Mouth Elan corporation for the development of hot
dissolving tablets by using this technology. drink sachet products which is the combination
of medicine and vitamins for over to counter
10. NanoCrystal Technology (Elan (OTC) medication purpose. Hot drink sachet
Corporation): when added to boiling water it produces
NanoCrystal technology has been developed pleasant flavored solutions with effervescent
by Elan Corporation. Name itself defines that granules. Mouth dissolving tablets prepared by
it is developed by decreasing the particle size this technology is useful for the treatment of
and increases the surface area which results in cold and flu.
the increased dissolution rate and
bioavailability of the drug. In this technology 13. Fast Melt (Elan Corporation)[24]
particle size of the drug should be less than Fast melts tablets are prepared by using
1000 nm in diameter. Particle size of the drug combination of effervescent base and active
can be decreased by wet milling process. ingredient. These type of tablets are highly
Mouth dissolving wafers are prepared by porous in nature when place in the mouth
mixing of nano crystal colloidal dispersions of dissolves rapidly on the tongue and avoid first
drug substance with water soluble GRAS pass effect and helps in the increasing the
(Generally Regarded as Safe) ingredients and bioavailability of the drug. Fast melt tablets
poured into blisters and lyophilized. Wafers show approximately 15 to 30 seconds
prepared by this technology shows quick disintegration time. Fast melts tablets shows
disintegration when come in contact with the improved patient compliance. Fast melts
water. tablets are helpful in such cases like where on
set of action is required.
Advantages:
 This technology highly useful for the highly 14. Multiflash (Prographarm)[25]
potent and hazardous materials because it In this technology tablet is manufactured by
avoids manufacturing operations such as using coated micro granules and fast
granulation, blending, and tableting, which disintegrating excipients. tablets prepared by
generate large quantities of aerosolizedpowder using this technique disintegrates quickly in
and present much higher risk of exposure. the oesophagus without mucosal adhesion.

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Following Table-1 Describes the Patented formulated using basic technologies.


Technologies and their Brand Names which are

Table-1: List of Marketed Products and Patented Technologies[25-29]


Patented Basis of technology Active ingredient Brand name Drug release
technology
Zydis Lyophilization Loratidine Claritin reditab and Dissolves in 2 to 10
Dimetapp quick dissolve sec.
Orasolv Direct compression Paracetamol Tempraquicklets, Disintegrates in 5 to
zolmitriptan Zolmigrepimelt 45 sec
Durasolv Direct compression Hyoscyamine sulfate NuLev,Zolmig Disintegrates in 5-45
zolmitriptan ZMT sec
Wowtab Direct compression Famotidine Gaster D Disintegrates in 5-45
sec
Flashdose Cotton candy process Tramadol HCl Relivia flash dose Dissolves within 1
minute
Flashtab Direct compression Ibuprofen Nurofen Flash Tab Dissolves within 1
minute
Quicksolv Lyophilization Cisapride monohydrate Propulsidquicksolv
---
risperidone Risperdal MTab
Lyoc Lyophilization Phloroglucinol SpasfonLyoc
---
hydrate
Ziplets Direct compression Ibuprofen Cibalgina due fast ---
Advatab Microcaps and diffuscap Cetrizine Adva Tab cetrizine, Disintegrates in less
CR technology paracetamol Adva Tab paracetamol than 30 secs.
Oraquick Micromask taste Hyoscyamine sulfate Hyoscyamine sulfate
---
masking ODT ODT
Following Table-2 describes the marketed formulations along with category.

Table-2: Marketed Formulations along with Category[30-31]


API Trade name Category
Piroxicam Felden fast melt NSAID
Loratidine Claritin redi Tab Antihistamine
Rizatriptan Maxalt MLT Migrane
Olanzapine Zyprexia Antipsychotic agent
Famotidine Pepcid RPD Antiulcer
Ondansetron Zofran ODT Anti-emetic
Zolmitriptan Zoming-ZMT Anti-migraine
Selegilline Zeplar TM Parkinson’s disease
Acetaminophen TempraQuiclets Analgesic
Paracetamol Febrectol Anti- pyretic and analgesic
Nimesulide Nimulid MDT NSAID
Rofecoxib Torrox MT Used in treatment of osteoarthritis
Olanzapine Olanexinstab Antipsychotic agent
Montelukast Romilast Anti-allergic drug
Diphenhydramine Benadryl Fastmelt Allergy, sinus pressure relief
and pseudoephedrine
Cisapride monohydrate PropulsidQuicksolv Gastrointestinal prokinetic agent
Risperidone Risperdal MTab Schizophrenia
Ibuprofen NurofenFlashTab) NSAID
Paracetamol TempraQuicklets Anti- pyretic and analgesic
Zolmitriptan ZolmigRepimelt Anti-migraine
Ibuprofen CibalginaDueFast NSAID
Tramadol HCl Relivia Flash dose Analgesic
Hyoscyamine Sulfate Hyoscyamine Sulfate ODT Anti-ulcer

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IAJPS 2018, 05 (02), 890-902 R. Santosh Kumar and Sahithi Mudili ISSN 2349-7750

CONCLUSION: 10.Yarwood RJ, Kearny P and Thomson AR. Process


Mouth dissolving tablets have better patient for preparing solid pharmaceutical dosage forms. US
acceptance and offer improved biopharmaceutical Patent 1998; No.5738875.
properties, improved efficacy and better safety as 11.B. Perissutti, F. Rubessa, M. Moneghini and D.
compared with conventional oral dosage forms. By Voinovich, Formulation design of carbamazepine
using new manufacturing technologies, many drugs fast-release tablets prepared by melt granulation
can be formulated in the form of mouth dissolving technique, Int. J. Pharm. 2003; 256 (1):53–63
tablets to provide the advantages of liquid medication 12.Y. Kuno, M. Kojima, H. Nakagami, E.
in the form of solid preparation. The key to mouth Yonemochi and K. Terada, Effect of the type of
dissolving tablets formulations is fast disintegration, lubricant on the characteristics of orally
dissolution, or melting in the mouth, and this can be disintegrating tablets manufactured using the phase
achieved by producing the porous structure of the transition of sugar alcohol, Eur. J. Pharm.
tablet matrix or adding superdisintegrant and/or Biopharm.2008;69 (3):986–92.
effervescent excipients. Among all conventional 13.Shukla D, Chakraborty S, Singh S, Mishra B.
technologies lyophilization technique is the most Mouth dissolving tablets: An overview of
useful technique for the formulation of mouth formulation technology. Sci. Pharm 2009; 76(2):309-
dissolving tablets. In lyophilization technique we can 26.
formulate heat sensitive drugs and biologics with 14.Seager H. Drug delivery product and the Zydis
lower disintegration time where as in other fast dissolving dosage form. J Pharmacol
techniques like heat moulding, spray drying requires Pharmacother1998; 50:375-82.
high amount of temperature for the formulation of 15.Lafon L. Galenic form for oral administration and
mouth dissolving tablets. its Method of preparation by lyophilization of an oil-
in-water emulsion 1985; Euro. Patent 0,159,237.
REFERENCES: 16.Lafon L. Galenic form for oral administration and
1.Bandari RK, Mittapalli R, Rao YM. Orodispersible its Method of preparation by lyophilization of an oil-
tablets: an overview. Asian J Pharm Sci 2008; 2(1):2- in-water emulsion 1985; Euro. Patent 0,159,237.
11. 17.Agarwal V, Kothari BH, Moe DV, Khankari RK.
2.S. Corveleyn and J. P. Remon, Formulation and Drug delivery: Fast-dissolve systems. Encyclopedia
production of rapidly disintegrating tablets by of pharmaceutical technology, Informa Healthcare
lyophilization using hydrochlorothiazide as a model 2006, New York, USA.
drug, Int. J. Pharm. 1997; 152 (1): 215–25. 18.Debjit B, Chiranjib, Jaiswal J, Dubey V, Chandira
3.Dobetti L. Fast melting tablets: Development and M. Fast dissolving tablet: A review on revolution of
technologies. Pharmaceutical Technology. 2001; 44- novel drug delivery system and new market
50. opportunities. Scholars research library. Pharm Lett
4.A. Modi and P. Tayade, Enhancement of 2009;1(2):262-76.
dissolution profile by solid dispersion (kneading) 19.Wehling F, Schuehle S, Madamala N.
technique, AAPS PharmSciTech.2006; 7(3) Article Effervescent dosage form with microparticles
68. 1993;US Patent 5,178,878.
5.Koizumi KI, Watanabe Y, Morita K, UtoguchiN, 20.Kaushik D, Dureja S, Saini TR. An overview of
Matsumoto M. New method for preparing high melt in mouth tablet technologies and techniques. SPI
porosityrapidly saliva soluble compressed tablets Pharma, 2004; 2(1):30-36.
using mannitol with camphor, a subliming material. 21.Cherukuri SR, Myers GL, Battist GE, Fuisz RC.
Int J Pharm 1997;152(1):127–31 Process for forming quickly dispersing comestible
6.D. M. Patel and M. M. Patel, Optimization of fast unit and product there from 1996; US Patent
dissolving etoricoxib tablet by sublimation technique, 5,587,172.
Indian J. Pharm. Sci.2008; 70 (1):71–76. 22.Liang A.C, Chen H. Fast-dissolving intraoral drug
7.Mizumoto T, Masuda Y and Fukui M. delivery systems. Expert Opinion. 2001; 11(6): 981-
Intrabuccally dissolving compressed moldings and 86.
production process thereof. US Patent 1996; No. 23.Verma R.K, Garg S. Current status of drug
5576014. delivery technologies and future directions. Pharm.
8.Bhaskaran S, Narmada GV. Rapid dissolving Tech. 2001; 25(2): 1-14.
tablets a novel dosage form. Indian Pharmacist 2002; 24.Ghosh T, Ghosh A, Prasad D. A review on new
1:9–12. generation Orodispersible tablets and its future
9.Patel BP. Fast dissolving drug delivery systems: An prospective. Int J Pharm Sci.2011; 3(1): 1-7.
update. pharmainfo.net.Bi 25.Goel H, ParshuramRai, VikasRana and Ashok K.
Tiwary. Orally Disintegrating Systems: Innovations

www.iajps.com Page 901


IAJPS 2018, 05 (02), 890-902 R. Santosh Kumar and Sahithi Mudili ISSN 2349-7750

in Formulation and Technology. Recent Pat Drug 29.Nagar P, Singh K, Chauhan I, Verma M, Yasir M,
Deliv Formul 2008, 2(3), 258-74. Khan A et al. Orally disintegrating tablets:
26.Patel GJ, Patel RJ, Patel PK, Bharadia PD, Pandya Formulation, preparation techniques and evaluation. J
VM, Modi DA. J Pharm and Cosmetology 2011; App Pharm Sci 2011; 1(4): 35-45.
1(2): 42-55. 30.Gajare GG, Bakliwal SR, Rane BR, Gujrathi NA,
27.Gavaskar B, Kumar SV, Sharan G, Nagaraju M, Pawar SP. Mouth dissolving tablets: A review. Int J
Rao YM. Present investigations and future prospects Pharm Res Dev 2011; 3(6): 280-96.
of oral disintegrating tablets: A review. Int J Pharm 31.Sammour OA, Hammad MA, Megrab NA.
Sci and Res 2010; 1(8): 14-28. Formulation and Optimization of Mouth Dissolve
28.Siddiqui MN, Garg G, Sharma P. Fast dissolving Tablets Containing Rofecoxib Solid Dispersion.
tablets: Preparation, characterization and evaluation: AAPS PharmSciTech. 2006; 7(2):162-69.
An Overview. Int J Pharm Sci Rev Res 2010; 4(2): 32.Fini A, Bergamante V, Ceschel GC, Ronchi C.
87-96. Fast dispersible/slow releasing Ibuprofen tablets. Eur
J Pharm Biopharm 2008; 69(1):335–41.

www.iajps.com Page 902